1. Field of the Invention
This invention relates to an improved method and new devices for the treatment of osteochondral defects. More particularly, the invention relates to a biosynthetic composite for osteochondral defect repair.
2. Description of the Related Art
Articular cartilage is the remarkably durable tissue that covers the articulating bone surfaces in our joints and permits pain-free movement by greatly reducing friction between bones and distributing stress. Damaged cartilage is a frequent problem in our population. Unfortunately, damaged articular cartilage has a limited ability to heal and can lead to premature arthritis.
Adult articular cartilage contains no blood supply, neural network or lymphatic drainage. As a result, partial thickness defects that do not reach the subchondral bone stimulate only a transient induction of chondrocyte replication and matrix production in the area adjacent to the wound. In young patients with focal and small lesions reparative/regenerative alternatives have been used with acceptable results as well as biological resurfacing in selected cases. Nevertheless, when a young patient presents with a large focal osteochondral defect due to trauma or avascular necrosis, and the defect of both bone and cartilage are too large to accept any regenerative procedure, there are currently no clinically proven treatment options.
Clinicians and researchers have been striving to develop methods of articular cartilage repair based on experimental studies showing the potential for cartilage repair through the use of transplanted chondrocytes, mesenchymal stem cells, or undifferentiated tissues containing stem cells or chondrocyte precursors (such as periosteum or perichondrium). In addition, periosteum tissue regenerates both cartilage and bone, and has been used successfully in biological resurfacing for the repair of damaged articular cartilage.
Currently, there are two general approaches to cartilage repair: (1) insertion of a new fragment of cartilage that has been generated in vitro, or (2) repair or regeneration of new cartilage in situ. The latter can be attempted either (a) by recruiting and inducing local cells with bioactive agents (growth factors) or (b) by implanting cells or tissue with the potential to form a new cartilage surface. Cells can be transplanted in a matrix such as an absorbable polymer or a suspension that is held in place with a cover. Cell transplantation can be performed using either undifferentiated chondrocyte precursor cells from periosteum, mesenchymal stem cells from bone marrow, or chondrocytes. Another approach is to transplant a tissue with chondrogenic potential, such as periosteum or perichondrium.
Attempts have been made to enhance the intrinsic potential of cartilage for self-repair using continuous passive motion, electricity, implanting scaffolds for repair and growth factors. Continuous passive motion is helpful for small defects, less than 3 millimeters in diameter, and electricity has not been proven to induce cartilage healing. Implanted scaffolds such as carbon fiber promote healing with fibrous tissue but not with cartilage. The local application of growth factors is very promising as a means of inducing local cells from the marrow and/or adjacent cartilage to participate in the repair process. Problems associated with intra-articular use of growth factors such as TGF-β include the undesirable side effects such as development of osteophytes. The potential benefit of enzymatic preparation of the defect surfaces in cartilage repair has also been demonstrated.
Periosteal grafts have been shown to have the potential for neochondrogenesis and can be used to repair articular cartilage defects in experimental animals (see FIG. 1 in which periosteum from the proximal medial tibia is sutured into a damaged area after debridement of the lesion down to the subchondral bone). The regenerated cartilage demonstrates acceptable long-term durability (see FIG. 2B). This new tissue has histological, histochemical and biochemical characteristics that are similar to those of normal articular cartilage. Although periosteum has the potential to produce bone via either endochondral or intramembranous ossification, periosteal neocartilage does not all calcify or ossify. In vivo studies show that newly formed cartilage from periosteum in osteoarticular defects in rabbits remained free of calcification at long-term follow-up (1 year in rabbits—see FIG. 2B). Endochondral replacement of the new cartilage did occur in the subchondral region originally occupied by bone. This process continued up to the level of the normal cartilage-bone junction (the tidemark), which was evident by the fourth week (see FIG. 2A), and remained stable for 1 year following surgery. Furthermore, the repair cartilage retained the appearance of hyaline articular cartilage, not epiphyseal cartilage, and did not show signs of hypertrophy. Thus, periosteal neocartilage is not predestined to either terminal hypertrophy or calcification. Calcification and/or ossification of cartilage appears to be regulated separately from chondrogenesis itself. Mechanical factors are important, because if the newly formed cartilage does not articulate with an opposing surface, such as occurs when the patella dislocates, the new tissue does ossify (see FIG. 2C).
In the treatment of full-thickness cartilage defects, there are several surgical resurfacing options available. The clinical outcomes of these procedures remain controversial. For example, debridement, subchondral penetration and abrasion arthroplasty are limited to the treatment of small lesions (<2 cm2) and result in a fibrous repair tissue with poor biomechanical properties.
Autologous chondrocyte transplantation and autologous osteochondral transplantation are probably the most extensively used alternative approaches for resurfacing lesions larger than 2 cm2 (<10 cm2). Autologous chondrocyte transplantation is a biological repair technique that has produced effective repair tissue in particular locations. However, the long-term viability of the hyaline-like repair tissue has not been proven. The viability of the transplanted cells has also been questioned. In addition, recent results have been reported that indicate that autologous chondrocyte transplantation is no better then either autologous osteochondral cylinder transplantation or microfracture techniques.
In the case of autologous osteochondral grafts, it has been shown in animal studies that the cartilage surface retains its structural and biochemical integrity. Additionally, clinical reports have demonstrated that when a well-standardized technique is performed and when indications are strictly followed, the results are promising and reproducible. However, there is still great concern regarding the donor site morbidity with 50-80% of patients reporting symptoms attributable to the donor site. Furthermore, progressive deterioration of the cartilage surrounding the donor site and involving weight bearing surface areas remains a main concern with this technique.
Thus, the development of a composite with the biochemical and mechanical properties of an autologous osteochondral graft with better integration properties and without the need for osteochondral graft harvesting would be very attractive.
Open cell tantalum structures have been developed for potential application in reconstructive orthopedics and other surgical disciplines (see, e.g., U.S. Pat. No. 5,282,861). The material has high and interconnected porosity with a very regular pore sharp and size. It can be made into complex shapes and used either as a bulk implant or as a surface coating. “Trabecular metal” has been shown to permit physiologic bone in growth and healing. In transcortical implant studies, new bone rapidly infiltrated the trabecular metal. The pore size and high volume porosity of trabecular metal supports vascularization and rapid secure soft tissue ingrowth (see FIG. 3 in which the left photograph shows bone ingrowth at 4 weeks and the right photograph shows fibrous tissue ingrowth at 4 weeks).
The mechanical properties of this material when tested as a porous scaffold had an elastic modulus (˜3 GPa) and compressive strength (˜50-80 MPa) in-between those of cortical (˜15 GPa/130-150 MPa) and trabecular bone (˜0.1 GPa/˜10-50 MPa) and had an elastic modulus resembling that of subchondral bone (˜2 GPa). It also had a high ductility during compressive testing and allowed plastic deformity. This “trabecular metal” has been shown to permit physiologic bone ingrowth and healing. In transcortical implant studies, new bone rapidly infiltrated and remodeled into the trabecular metal. The pore size and high volume porosity of trabecular metal also supports vascularization and rapid secures soft tissue ingrowth.
Periosteum, the connective tissue that surrounds bones, has the capacity to regenerate both cartilage and bone. This unique tissue contains two discrete layers: the inner cambium layer which is believed to contain the undifferentiated mesenchymal stem cells responsible for fracture repair and the outer fibrous layer. Periosteum has been used successfully in biological resurfacing for the repair of damaged articular cartilage. For deep osteochondral defects, a bone graft can be used to replace the damaged subchondral bone. However, potential problems with the use of bone grafts include obtaining grafts of the appropriate size and shape, graft-site morbidity, and tissue integration with the surrounding tissue.
Therefore, there is no satisfactory treatment at the present time for deep osteochondral defects. Accordingly, there is a need for an improved method and new devices for the treatment of osteochondral defects.